i wouldn;t hazard a guess regarding alzheimer's. its just
i wouldn;t hazard a guess regarding alzheimer's. its just way too complex and the role of ccr5 is complicated there from what i have read in the past and reviewing a bit just now. there are plenty of positive studies regarding ccr5 inhibition and neurodegeneration and memory, but its all very complicated.
there is a lot of ccr5 inhibition activity vs alzheimer's and related conditions- which is good that others seem to think it has a chance but also potentially bad because there is competition.
maraviroc is being studied vs 3 areas of alzheimer's / dementia currently. in 3 different countries. post-stroke dementia in israel, memory linkage at ucla and tau protein aggregates in the uk. and there are multiple MOAs in play with ccr5 inhibition and alzheimer's / neurodegenerative decline / memory loss.
and before we conclude "oh well, maraviroc stinks, we'll crush that", there is research indicating that partially blocking the ccr5 receptor may be better than blocking completely. ccr2 may be a way for the disease to compensate when ccr5 is thoroughly blocked, similar to the elevated pd-1 in tnbc. and ccr2 expression has negative effects for alzheimr's.
dual acting molecules vs ccr5 / ccr2 meanwhile have been shelved for different reasons and so that competition really doesn;t exist.
and rounding all that out, aphios is trying to get beyond the ccr2 issue by using nanoparticles to carry maraviroc across the BBB. interest in solving that problem is encouraging as leron crosses the BBB. but then again it also loses potency across the BBB. but then again again, maybe that isn;t such a bad thing in alzheimer's. but then again again again maybe it is!
its complicated!
there's a ccr5 paradox, there's a potential need for dual inhibition, and alzheimer's was already quite a puzzle to be solved.
there;s even a next-gen maraviroc called a14 developed in china for improved BBB permeability. but that is very early in its development. not a a factor.
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